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Text
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URL Address
<a href="http://doi.org/10.1038/nbt750" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/nbt750</a>
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Pages
1103-1110
Issue
11
Volume
20
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Title
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Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons
Publisher
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Nature Biotechnology
Date
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2002
2002-11
Subject
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1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine mptp; adult brain; Biotechnology & Applied Microbiology; central-nervous-system; dopaminergic; gene-transfer; growth factor; juvenile neocortex; mouse-brain; neurotoxicity; parkinsons-disease; replacement
Creator
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Ourednik J; Ourednik V; Lynch W P; Schachner M; Snyder E Y
Description
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We investigated the hypothesis that neural stem cells (NSCs) possess an intrinsic capacity to "rescue" dysfunctional neurons in the brains of aged mice. The study focused on a neuronal cell type with stereotypical projections that is commonly compromised in the aged brain-the dopaminergic (DA) neuron. Unilateral implantation of murine NSCs into the midbrains of aged mice, in which the presence of stably impaired but nonapoptotic DA neurons was increased by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was associated with bilateral reconstitution of the mesostriatal system. Functional assays paralleled the spatiotemporal recovery of tyrosine hydroxylase (TH) and dopamine transporter (DAT) activity, which, in turn, mirrored the spatiotemporal distribution of donor-derived cells. Although spontaneous conversion of donor NSCs to TH+ cells contributed to nigral reconstitution in DA-depleted areas, the majority of DA neurons in the mesostriatal system were "rescued" host cells. Undifferentiated donor progenitors spontaneously expressing neuroprotective substances provided a plausible molecular basis for this finding. These observations suggest that host structures may benefit not only from NSC-derived replacement of lost neurons but also from the "chaperone" effect of some NSC-derived progeny.
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<a href="http://doi.org/10.1038/nbt750" target="_blank" rel="noreferrer noopener">10.1038/nbt750</a>
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Journal Article
1-Methyl-4-phenyl-1
2
2002
3
6-tetrahydropyridine mptp
adult brain
Biotechnology & Applied Microbiology
central-nervous-system
dopaminergic
gene-transfer
growth factor
Journal Article
juvenile neocortex
Lynch W P
mouse-brain
Nature Biotechnology
Neurotoxicity
Ourednik J
Ourednik V
parkinsons-disease
Replacement
Schachner M
Snyder E Y